Musculoskeletal Gene Therapy Research Laboratory, Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905, USA.
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Int J Mol Sci. 2024 Nov 12;25(22):12130. doi: 10.3390/ijms252212130.
Aging is a major risk factor for osteoarthritis (OA), but the specific mechanisms connecting aging and OA remain unclear. Although chondrocytes rarely divide in adult articular cartilage, they undergo replicative senescence in vitro, offering a model to study aging-related changes under controlled conditions. OA cartilage was obtained from an 80-year-old male and a 72-year-old female, while normal cartilage was sourced from a 26-year-old male. Chondrocyte cultures were established and sub-cultured to their Hayflick limit. Bulk RNA sequencing on early- and late-passage human articular chondrocytes identified transcriptomic changes associated with cellular aging. Early-passage OA chondrocytes already showed senescent phenotypes, unlike normal chondrocytes. All three cultures underwent 30 population doublings before replicative exhaustion, at which point all cells displayed senescence. During this process, cells lost their ability to form cartilaginous pellets. Differential gene expression analysis revealed distinct transcriptomic profiles between early- and late-passage chondrocytes and between normal and OA-derived cells. Genes related to matrix synthesis, degradation, inflammation, and the senescence-associated secretory phenotype (SASP) showed significant expression changes. Despite being a small pilot study, these findings suggest that further research into the molecular and metabolic changes during chondrocyte senescence could provide valuable insights into OA pathobiology.
衰老是骨关节炎（OA）的一个主要危险因素，但将衰老与 OA 联系起来的具体机制仍不清楚。尽管成年关节软骨中的软骨细胞很少分裂，但它们在体外经历复制性衰老，为在受控条件下研究与衰老相关的变化提供了模型。OA 软骨取自一名 80 岁男性和一名 72 岁女性，而正常软骨取自一名 26 岁男性。建立了软骨细胞培养物并进行传代培养至 Hayflick 限制。对早期和晚期传代的人关节软骨细胞的 bulk RNA 测序鉴定了与细胞衰老相关的转录组变化。与正常软骨细胞不同，早期传代 OA 软骨细胞已经表现出衰老表型。所有三种培养物在复制耗尽之前都经历了 30 个群体倍增，此时所有细胞都显示出衰老。在此过程中，细胞失去了形成软骨球的能力。差异基因表达分析显示，早期和晚期传代软骨细胞之间以及正常和 OA 来源细胞之间存在明显的转录组谱差异。与基质合成、降解、炎症和衰老相关 secretory 表型（SASP）相关的基因表达发生显著变化。尽管这是一项小型试点研究，但这些发现表明，进一步研究软骨细胞衰老过程中的分子和代谢变化可能为 OA 病理生物学提供有价值的见解。
